LIFR-α-dependent adipocyte signaling in obesity limits adipose expansion contributing to fatty liver disease

Tong Guo, Arun Gupta, Jinhai Yu, Jorge Z. Granados, Aakash Y. Gandhi, Bret M. Evers, Puneeth Iyengar, Rodney E. Infante

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


The role of chronic adipose inflammation in diet-induced obesity (DIO) and its sequelae including fatty liver disease remains unclear. Leukemia inhibitory factor (LIF) induces JAK-dependent adipocyte lipolysis and altered adipo/cytokine expression, suppressing in vivo adipose expansion in normal and obese mouse models. To characterize LIF receptor (LIFR-α)-dependent cytokine signaling in DIO, we created an adipocyte-specific LIFR knockout mouse model (Adipoq-Cre;LIFRfl/fl). Differentiated adipocytes derived from this model blocked LIF-induced triacylglycerol lipolysis. Adipoq-Cre;LIFRfl/fl mice on a high-fat diet (HFD) displayed reduced adipose STAT3 activation, 50% expansion in adipose, 20% body weight increase, and a 75% reduction in total hepatic triacylglycerides compared with controls. To demonstrate that LIFR-α signals adipocytes through STAT3, we also created an Adipoq-Cre;STAT3fl/fl model that showed similar findings when fed a HFD as Adipoq-Cre;LIFRfl/fl mice. These findings establish the importance of obesity-associated LIFR-α/JAK/STAT3 inflammatory signaling in adipocytes, blocking further adipose expansion in DIO contributing to ectopic liver triacylglyceride accumulation.

Original languageEnglish (US)
Article number102227
Issue number3
StatePublished - Mar 19 2021


  • Animal Physiology
  • Biological Sciences
  • Cell Biology
  • Cellular Physiology
  • Endocrinology

ASJC Scopus subject areas

  • General


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